Alltrna is the latest in a growing number of startups with plans to develop therapies based on transfer RNA (tRNA), a family of RNA molecules that play a vital role in building proteins. The Cambridge, Massachusetts-based company has launched from stealth with up to $50 million committed from Flagship Pioneering, the investment firm that helped found the messenger RNA (mRNA) company Moderna in 2010.
Although tRNA is vital to life, the molecule has received little interest from the drug industry until recently. mRNA is a passive molecule that encodes instruction for making proteins. In contrast, tRNA is an active molecule that helps translate the mRNA code. tRNA reads three letters of an mRNA strand at a time—a unit called a codon—and transfers a corresponding amino acid to the ribosome, our cells’ protein making machinery.
Some scientists and biotech investors, including leaders at Alltrna, think that tinkering with tRNA could provide a new way to treat diseases in which mutations in mRNA cause cells to make faulty proteins. Lovisa Afzelius, founding CEO of Alltrna, says the startup is engineering tRNA that can target mRNA mutations and transfer the appropriate amino acid to the ribosome, thus restoring the production of normal proteins.
Alltrna joins at least three companies developing engineered tRNA molecules to restore protein production in genetic diseases. ReCode Therapeutics is focused on cystic fibrosis, Shape Therapeutics has a program for a neurodevelopmental disorder called Rett syndrome, and Tevard Biosciences is working on genetic epilepsies including Dravet syndrome. The startups have collectively raised more than $320 million, although ReCode and Shape are also working on other RNA-based technologies.
Tevard and Alltrna are focused solely on tRNA. Theonie Anastassiadis, cofounder and chief innovation officer of Alltrna, says the startup also hopes to manipulate the ratios of different natural tRNAs found in cells to control translation and either boost or reduce protein production. A third Alltrna program is focused on a class of poorly-understood molecules called tRNA-derived fragments, which are involved in regulatory processes and implicated in multiple diseases, including cancer. “The biology is fascinating and completely overlooked,” Anastassiadis says.
Alltrna isn’t disclosing which diseases it will focus on or a timeline for getting a tRNA therapy into a clinical trial. But Afzelius says the firm will “go broad in our areas of applicability.”
Like the other companies developing tRNA therapies, Alltrna contends it can potentially use one tRNA therapy to treat several diseases caused by similar or identical mRNA mutations. Afzelius goes so far as to say that a single tRNA medicine could be used “to treat thousands and thousands of diseases.”